The proposed work deals with the development and testing of oxygen-binding iron chelates including those that are purely synthetic and others derived from hemaglobin. In collaboration with scientists at Oxford, the synthesis of reversible oxygen-binding iron chelates will be pursued. These are modifications of the porphyrin molecule utilizing a " strapped" or "capped" structure to protect the iron from irreversible oxidation. Functional groups in the molecule will allow attachment of larger groups which will increase molecular size and, thus, lengthen circulation dwell time. The effectiveness and safety of these chelates in transporting oxygen in vivo and in vitro will be determined. The metabolic fate of both the iron and the rest of the molecule will be established. Stroma-free hemoglobin will be prepared and used as such or converted to modified hemoglobins for oxygen-binding studies and biological testing. These modifications will involve the coupling of the hemoglobin (Hb) with compounds such as high molecular weight polymers and hydroxyethyl starch (HES). The linkages between the Hb and HES or other molecules will be varied. Different ratios of Hb to HES will be used to prepare a variety of complexes having widely differing oncotic properties. The usefulness of these complexes in blood replacement in vivo and for organ perfusion in vitro will be investigated. Their metabolic fate will also be ascertained.